The present invention relates generally to cancer treatment methods. More particularly, the invention describes exposing a cancer subject to a remote conditioning procedure. As a result of such procedure, certain biologically active substances may be upregulated or released that may beneficially affect the cancer subject such as for example slow the proliferation of malignant cells throughout the body of the cancer subject.
Cancer is a group of diseases involving abnormal cell growth and proliferation. In 2012 about 14.1 million new cases of cancer occurred globally. It caused about 8.2 million or 14.6% of all human deaths. The most common types of cancer in males are lung cancer, prostate cancer, colorectal cancer, and stomach cancer, and in females, the most common types are breast cancer, colorectal cancer, lung cancer, and cervical cancer. Skin cancer is not included in these statistics and if it were it would account for at least 40% of cases. The financial costs of cancer have been estimated at $1.16 trillion US dollars per year as of 2010. Despite tremendous progress in the treatment methods, cancer subjects continue to experience pain and suffering as well as early death as a result of this disease necessitating further research into treatment modalities.
Two most widely used treatment methods for various cancers include radiation therapy and chemotherapy. However, these treatments have significant side effects as they affect both malignant as well as healthy cells. Indiscriminate cell death causes both a health benefit (tumor suppression) as well as harm caused by loss of healthy tissues. New treatment methods are therefore needed that do not cause harm to the cancer subject while continuing to provide health benefits.
Cancer in general is known to have five major development steps: initiation, promotion, malignant conversion, progression, and metastasis. Many factors influence the development and proliferation rate of cancers: some inhibit tumor development (tumor suppressors), and some promote cancer development (cancer inducers). The formation of cancer is the combined interaction of both tumor suppressors and cancer inducers. Scientists have been trying to elucidate the molecular mechanisms that cause cancer development and cancer prevention for a long time. Although several genes, including oncogenes and tumor suppressor genes, have been identified in human and/or other model animal genomes, the exact mechanism of cancer formation is yet to be identified. A recently identified class of non-protein-coding small RNAs, microRNAs (also referred to as miRNAs or miR), may provide new insight in cancer research. A recent study demonstrated that more than 50% of miRNA genes are located in cancer-associated genomic regions or in fragile sites, suggesting that microRNAs may play an important role in the pathogenesis of human cancers.
When cells exhibit abnormal growth and loss of apoptosis function, it usually results in cancer formation. Several recent studies indicate that microRNAs regulate cell growth and apoptosis. For example, microRNA-15 and microRNA-16 induce apoptosis by targeting antiapoptotic gene B cell lymphoma 2 (BCL2) mRNA, which is a key player in many types of human cancers, including leukemias, lymphomas, and carcinomas. Also demonstrated was that aberrant expression of microRNA-278 in developing eyes causes massive overgrowth in Drosophila, partially due to inhibition of apoptosis by miR-278. This suggests that microRNAs are involved in cancer formation through regulation of cell growth and apoptosis.
Lung cancer is one of the most common cancers of adults. It is also the leading cause of cancer-related deaths in many economically developed countries. Emerging evidence suggests that at least microRNA let-7 and perhaps others may control lung cancer development, or at least play a critical role in its pathogenesis. Another example of microRNA involvement comes from breast cancer research. Breast cancer is one of the most important cancers in adult females. Evaluation of hundreds of microRNA expression profiles led to a discovery that the microRNA expression patterns were significantly different between normal and neoplastic breast tissues; microRNA-125b, microRNA-145, microRNA-21, and microRNA-155 were shown to be significantly reduced in breast cancer tissues. Also observed was the fact that the expression of microRNAs was correlated with specific breast cancer bio-pathologic features, such as tumor stage, proliferation index, estrogen and progesterone receptor expression, and vascular invasion.
Evidence continues to emerge that aberrant expression of various microRNAs (whether increased or decreased levels as compared with normal tissues) plays a major role in tumor growth and spreading.
Because microRNAs function as oncogenes or tumor suppressors, it might be possible to inject microRNAs to regulate cancer formation, similar to the use of antisense mRNAs and RNAi, which are widely used as tools for studying gene functions and in some case of gene therapy. Artificial microRNAs could be synthesized to down-regulate oncogenes and prevent the formation of cancer. In fact, some short-term animal studies have confirmed that hypothesis. However, there is a long way to go before artificial microRNAs could be used as cancer therapeutic tools and microRNA therapy for clinical purposes. To achieve this goal, several obstacles need to be overcome. First, specific microRNAs in a specific type of cancer should be identified; only when the specific microRNAs are identified and their action mechanisms were elucidated in a specific cancer, physicians can manipulate these microRNAs for therapeutic purposes. How to deliver these microRNAs into targeted tissues and keep their continuous activity is another obstacle. It may also be quite difficult to manufacture such compounds in a form of an ingestible pill as microRNAs may not survive the harsh acidic environment of the digestive system. Finally, safety considerations need to be addressed as various microRNAs may have an impact on various genes elsewhere in the body of the cancer subject.
Accordingly, there is a need to overcome the limitations of the prior art and to provide novel cancer treatment methods designed to minimize healthy tissue damage or other negative health consequences of traditional cancer treatments, while providing meaningful health benefits to the cancer subject.
There is also a need to provide safe, non-invasive novel cancer treatment methods that can be applied to cancer subjects by medical professionals or even self-applied.